Chemotherapeutics such as cisplatin are indispensable to the treatment of cancer. However, the chemotherapeutics cause side effects such as vomiting and hence make it difficult to continue the treatment.
Recently, it has become known that the occurrence of vomiting is associated with one of receptors of serotonin [5-hydroxytryptamine, hereinafter referred to as "5-HT"]. 5-HT is one of neurotransmitters in the living body and receptors of 5-HT have been classified into three groups, 5-HT.sub.1, 5-HT.sub.2 and 5-HT.sub.3. Among them, 5-HT.sub.3 receptor is associated with vomiting due to chemotherapeutic treatment of cancer. That is, 5-HT is released by administration of the chemotherapeutics and the released 5-HT is bound to the abdominal 5-HT.sub.3 receptor, and thereby the chemical receptor trigger in the bulb fourth ventricle is stimulated via the abdominal vagus nerve, and then the vomiting center is stimulated to induce vomiting.
It has been reported that Ondansetron (GR38032F, see the following formula) having 5-HT.sub.3 antagonistic activity is effective for inhibition of vomiting caused by the administration of the chemotherapeutics such as cisplatin [Cancer. Chemother. Pharmacol., 23, 389-391 (1989)]. ##STR2##
On the other hand, there has already been known the use of 2-(4-methyl-1-piperazinyl)benzimidazole derivatives as a drug. For example, Japanese Patent First Publication No. 50-126682 discloses 2-(4-methyl-1-piperazinyl)benzimidazole derivatives having analgesic and antiinflammatory activities, and 1-methyl-2-(4-methyl-1-piperazinyl)benzimidazole (Compound A) etc are exemplified. However, the 5-HT.sub.3 antagonistic activity and the resulting antiemetic activity of 2-(4-methyl-1-piperazinyl)benzimidazole derivatives have not yet been known (see Experiment 1 disclosed hereinafter).
The present inventors have conducted a variety of studies for developing a novel antiemetic agent having a strong and long-lasting inhibitory activity against vomiting due to chemotherapeutic treatment of cancer with cisplatin etc. based on the 5-HT.sub.3 antagonistic activity.